Tumor Characteristics Research Articles

Differential expression of the SLC34A2 gene in different histological subtypes of ovarian carcinomas

BACKGROUND: Patients with ovarian carcinoma demonstrate different sensitivity to chemotherapy; therefore, to increase the effectiveness of treatment, it is necessary to take into account the characteristics of each patient's tumor, including the histological subtype. AIM: To search for new molecular markers of ovarian cancer by analyzing the expression of candidate genes, including BAX, SLC34A2, MUC16, CD300A, and XKR8, in ovarian carcinomas of different histological subtypes. MATERIAL AND METHODS: Analysis of the expression of the BAX, SLC34A2, MUC16, CD300A, and XKR8 genes in 33 carcinomas taking into account their histological subtypes was performed using real-time polymerase chain reaction. Tumor samples from patients with ovarian carcinoma were obtained from the Blokhin National Medical Research Center of Oncology (Moscow) and the Republican Clinical Oncology Dispensary (Kazan) and divided into groups by histological subtypes: serous of high (n=16) and low (n=6) grade malignancy, endometrioid (n=8) and mucinous (n=3). Additional analysis was performed using microarray data from the Gene Expression Omnibus open database to determine the expression of selected candidate genes in ovarian carcinomas of different histological subtypes. The dataset included 4 normal ovary samples and 95 ovarian carcinoma samples of different histological subtypes: serous (n=41), endometrioid (n=37), and mucinous (n=13). Statistical analysis of the data was performed using Prism software. Nonparametric Dunn's test was used to compare gene expression in several patient groups. RESULTS: The expression level of the SLC34A2 gene was increased in low-grade serous carcinomas (p=0.0257) compared to mucinous carcinomas. Using bioinformatics analysis, we found increased expression of the SLC34A2 gene in serous (p=0.0023) and endometrioid ovarian carcinomas (p=0.0355) compared to normal ovarian tissues. CONCLUSION: The SLC34A2 gene can be considered as a potential molecular marker for differential diagnosis of ovarian cancer histological subtypes and a target for therapy of patients with low-grade serous ovarian carcinoma.

Fine-needle aspiration and effusion cytology of thoracic SMARCA4-deficient undifferentiated tumor and SMARCA4-deficient non-small cell lung carcinoma: A multi-institutional experience with 27 patients.

Thoracic switch/sucrose nonfermentable-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4)-deficient (SD) malignancies, including SD undifferentiated tumor (SD-UT) and SD non-small cell lung carcinoma (SD-NSCLC), have been recently described. The cytologic features of these neoplasms in fine-needle aspiration (FNA) and effusion specimens have rarely been reported in the literature. This study aimed to describe and compare the spectrum of cytologic, immunohistochemical, and clinical features ofthese high-grade malignancies recently encountered at the participating institutions. This study documented clinical and imaging characteristics of tumors from 27 patients. Sixteen cytomorphologic features and immunohistochemical findings were compared between SD-UT and SD-NSCLC samples. Twenty three FNAs, two bronchial brushings, and two pleural fluids were evaluated, including 17 SD-UT cases (mean patient age, 70 years) and 10 SD-NSCLC cases (mean patient age, 62 years). Both malignancies presented with large thoracic masses and/or hilar/mediastinal lymphadenopathy. All SD-UT cytologic samples had a discohesive or mixed cohesive-discohesive architecture, and most (13 of 17) showed predominant rhabdoid or mixed rhabdoid-epithelioid features. Most SD-NSCLC cytologic samples (nine of 10) were either cohesive or mixed cohesive-discohesive and had a predominantly epithelioid morphology (eight of 10). Keratins and claudin-4 were negative or focally positive in SD-UT samples, whereas they were diffusely positive in SD-NSCLC samples. Both malignancies were negative for TTF-1 and p40/p63 and showed loss of expression of SMARCA4. Although there is considerable clinical and cytopathologic overlap between SD-UT and SD-NSCLC, some key features allow for their distinction. SD-UT is mostly discohesive with rhabdoid or mixed rhabdoid-epithelioid features, whereas SD-NSCLC often has cohesive epithelioid morphology. The combination of clinical presentation, cytomorphology, and immunohistochemistry is essential for a definitive diagnosis.

Response to Bridging Therapy as a Prognostic Indicator of Post-Transplantation Hepatocellular Carcinoma Recurrence and Survival: A Systematic Review.

Liver transplantation (LT) is one of the most effective treatments for hepatocellular carcinoma (HCC) in cirrhotic livers. Neoadjuvant bridging treatment in patients qualifying and listed for LT is advised but is still debatable owing to the low level of evidence. The aim of this study was to perform a systematic review to assess the prognostic value of bridging therapy, in terms of radiological and histopathological examination outcomes, for survival after LT. The systematic review was performed according to the PRISMA 2020 guidelines. The MEDLINE and Web of Science databases were searched. In total, five studies were included. An evaluation with the ROBINS-I resulted in studies classified as the following: moderate risk of bias (n = 1) and serious risk of bias (n = 4). The results of the analysis indicated that favorable LT outcomes were most common with complete response or partial radiological response. Poor radiological response or progressive disease during bridging treatment was generally associated with worse overall LT survival. There were not enough data to support the use of this approach to achieve a complete pathologic response. Radiological, pathological, histological, cellular, and molecular tumor features should be included in future LT qualification models.

Real‐World Outcomes of Patients Treated With Gemcitabine Using Standardized Dose and Rate and Docetaxel for Advanced Soft Tissue Sarcoma in an Australian Sarcoma Center

ABSTRACTBackgroundGemcitabine and docetaxel (GD) is a common chemotherapy regimen for metastatic soft tissue sarcoma (STS). The GeDDiS trial compared GD with doxorubicin in the first‐line setting, using gemcitabine 675 mg/m2 over a prolonged rate of 90 min—reporting a 20% response rate and 5.4‐month median progression‐free survival (PFS). We aimed to examine the real‐world efficacy and toxicity of GD in our center, using a standardized dose of gemcitabine 900 mg/m2 over 30 min on Days 1 and 8 and intravenous docetaxel 75 mg/m2 over 60 min on Day 8 every 21 days.MethodsA retrospective analysis was conducted of patients with unresectable or metastatic STS receiving GD between July 2018 and October 2022. Data collected included patient and tumor characteristics, dose intensity, toxicity, response, PFS, and overall survival (OS).ResultsThirty‐eight patients were included. Median follow‐up was 19 months (range 3–30). Line of treatment (n) was first line (10), second line (13), ≥ third line (15). The median number of cycles was 6. Response rate was 42%, including 5% with a complete response. At the time of data collection, 33 patients had disease progression and 24 patients had died. PFS (median, 6‐month rate) was 4.5 months and 44%. OS (median, 12‐month rate) was 15 months and 65%. Grade 3/4 toxicity included anemia (21%), neutropenia (5%), thrombocytopenia (5%), and febrile neutropenia (3%).ConclusionThese data demonstrate the activity of gemcitabine using a standardized dose and rate with docetaxel comparable to other published data and favorable toxicity in a real‐life patient population despite altered gemcitabine dosing and a heavily pretreated patient population.

Abstract B029: Mapping the vascular walls of colorectal cancer

Abstract Introduction: Properties of tumor angiogenesis impact on tumor growth and composition of the tumor microenvironment. Tumor vessels are composed of pericytes and other mural cells. Detailed characterization of the cellular composition of the microvasculature can suggest functional vessel and case properties relevant for outcome, response to treatment and immune surveillance. Results: Based on single cell RNA-seq from three human stage II/III colon cancers and pilot in-situ multi-antibody staining of six tumors two main clusters of perivascular cells were identified; B1 (MCAM+, MYH11-) and B2 (MCAM+, MYH11+) cells. B1 cells displayed pericyte features including expression of RGS5, whereas B2 cells showed high expression of smooth muscle cell markers like ACTG2 and Desmin. Desmin-high B2 cells were predominantly located in muscular layers, whereas Desmin-low/MYH11-high B2 cells showed perivascular enrichment. An extended novel analyses workflow of digital image analysis was used to profile peri-endothelial composition in 19 intervals; 11 1-µm intervals from 0 to 10 µm and 8 5-µm intervals from 10 to 50 µm from endothelial areas. Each of these expansion areas was quantitated regarding density of PDGFRB+/- cells including B1/B2 cells, and a MYH11+/MCAM- cells. Density of macrophage subsets (CD68-positive subsets defined by CD163 and CD11c) were also quantitated. In general, B1 cells showed stronger spatial association with endothelial cells than B2 cells, and this spatial association was stronger for the PDGFRB+ B1 subset. Survival analysis indicated that prognostic relevance was strongest when PDGFRB+ (favorable prognosis) cells were closest to endothelial cells. Regarding perivascular macrophage density, M0 and transit M1/M2 macrophages were predominantly enriched in the peri-endothelial regions, whereas density of M1 and M2 increased gradually as distance from vessels increased. M2 density was overall associated with poor prognosis, whereas high density of other macrophage subsets overall was associated with good prognosis. Ongoing studies are using a clustering-based approach to identify vessel subsets, and prognosis associations are being consolidated in additional cohorts. Summary: This study provides a novel approach for high resolution profiling of perivascular status in CRC, and possibly other tumor types, that could be of specific importance to identify tumor features associated with response to angiogenesis-directed therapies. Citation Format: Linglong( 凌 龙 ) Huang( 黄 ), Mercedes Herrera, Jonas Sjölund, Vladimir Chocoloff, Simon Joost, Rasul M. Tabiev, Lina Wik Leiss, Carina Strell, Luis Nunes, Artur Mezheyeuski, David Edler, Anna Martling, Fredrik Pontén, Bengt Glimelius, Tobias Sjöblom, Maria Kasper, Kristian Pietras, Arne Östman. Mapping the vascular walls of colorectal cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B029.

Abstract C028: Decreased heterogeneity in immune interactions in oral cavity squamous cell carcinoma patients with recurrence

Abstract There have been improvements in clinical risk stratifications for oral cavity squamous cell carcinoma (OSCC) with the AJCC 8th edition staging system. Other studies suggest the addition of a metric of specific immune interactions in and around the tumor may be helpful to further stratify patients, with mixed findings. The advent of spatial imaging has allowed a global view for assessing tumor features in the context of all surrounding cell interactions. We hypothesize that the lack of architectural information could contribute to varied clinical outcomes in previous studies, such as tumor recurrence. This highlights how spatial technologies could aid in understanding the role of tissue architecture and its influence on biology and medicine. To study tissue remodeling spatially, we focused on multiplexed-ion beam imaging (MIBI), a spatial proteomics platform to visualize 40 immuno-onco proteins simultaneously. Our banked patient cohort consists of 20 recurrent and 49 non-recurrent OSCC primary surgery samples. Clinical metadata capturing pathologic stage, alcohol use, smoking history, survival data, and more were also collected. With our pathologist, we curated 290 field-of-views (FOVs) of matched primary tumors, uninvolved lymph nodes, and metastatic lymph nodes (if any). Downstream computational analysis using existing MIBI codebases augmented with in-house spatial analytics has revealed a robust spatial dataset. After using machine-learning algorithms to cell segment our images, we validated these assigned cells and marker staining to further annotate cell populations. When we analyzed direct cell interactions, there was a decrease in heterogeneity in immune interactions within recurrent patients compared to non-recurrent patients. To ascertain how the loss of these interactions affected recurrence prognosis, we investigated their prevalence within the tumor border vicinity. We hypothesize that the proximity and cell-cell interactions near the border will promote a tumor-suppressive environment. Utilizing centroid-to-centroid distance measurements, we distilled the top 30 cell-cell interactions within a 100-micron distance from the tumor border. Cell pairs involving macrophage tissue-resident memory cells and CD8 T memory resident cells were more abundant in recurrent patients, while pairs involving CD4 T regulatory and CD8 cells were found in non-recurrent patients. Reassuringly, cell pairings involving myeloid cells were upregulated in the recurrent cohort as expected. Interestingly, cancer-associated fibroblast cell pairings were upregulated indiscriminately in both patient sub- cohorts. This suggests that the impact of certain known immunosuppressive changes may contribute in varying amounts to disease control. Our data demonstrates differences in the architecture of tumors with known divergent outcomes, which suggests global tissue-level changes could be a predictive factor. Clinically, interrogating these interactions of interest could guide treatment escalation or de-escalation in the future. Citation Format: Connie J. Zhou, Jane Lee, Rebecca Jaszczak, Steven R. Long, Patrick K. Ha, Matthew H. Spitzer. Decreased heterogeneity in immune interactions in oral cavity squamous cell carcinoma patients with recurrence [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C028.

Analysis of positive predictors in diagnosing lung cancer on transthoracic and transbronchial procedure

Background: Lung cancer remains the most cause of death due to cancer. Due to high mortality rate of lung cancer, early diagnosis of lung cancer plays a very important role in therapeutic management. Clinical symptoms and tumor characteristics such as size and location are found to vary in lung cancer patients. Various modalities can be used to obtain materials or samples include transthoracic and transbronchial methods. Research was conducted to analyze positive predictors of cancer between transthoracic and transbronchial procedures in lung cancer patients. Methods: This research is an analytical observational study with a cross-sectional design in using secondary data through medical records from January 2022 to December 2023. Univariate analysis presents data in the form of frequency, mean and standard deviation. Bivariate analysis was carried out using chi-square and multivariate analysis using multiple logistic regression. The measure used as a predictor is the adjusted odds ratio. Inference or conclusion is based on the 95% confident interval and p value at the alpha value limit of 0.05. The entire data process above uses SPSS 26.0 statistical software Results: The total research subjects who met the research requirements were 111 patients. The characteristics of the research subjects were symptoms of cough (n=97; 87.4%), hemoptyisis (n=51; 45.9%), breathlessness (n=104; 93.7%) and chest pain (n=87; 78.4%), mostly peripheral tumor (n=70; 63.1%) and size >3 cm (n=103; 92.8%). Logistic regression analysis showed cough symptoms and peripheral tumor location each had an adjOR value of 5.247 (95% CI 1.432-19.552; p=0.013) and adjOR 0.088 (95% CI 0.034-0.229; p=0.000) for lung cancer positivity on transbronchial procedure. On transthoracic procedure, cough symptoms and peripheral tumor location respectively had an adjOR value of 0.190 (95% CI 0.051-0.703; p=0.013) and adjOR 11.407 (95% CI 4.374-29.747; p=0.000) for lung cancer positivity. Conclusions: Cough is a positive predictor of lung cancer in transbronchial procedures. Meanwhile, peripheral tumor location is a positive predictor of lung cancer in transthoracic procedures.

Visualizing the association between the location and prognosis of isocitrate dehydrogenase wild-type glioblastoma: a voxel-wise Cox regression analysis with open-source datasets.

This study examined the correlation between tumor location and prognosis in patients with glioblastoma using magnetic resonance images of various isocitrate dehydrogenase (IDH) wild-type glioblastomas from The Cancer Imaging Archive (TCIA). The relationship between tumor location and prognosis was visualized using voxel-wise Cox regression analysis. Participants with IDH wild-type glioblastoma were selected, and their survival and demographic data and tumor characteristics were collected from TCIA datasets. Post-contrast-enhanced T1-weighted imaging, T2-fluid attenuated inversion recovery imaging, and tumor segmentation data were also compiled. Following affine registration of each image and tumor segmentation region of interest to the MNI standard space, a voxel-wise Cox regression analysis was conducted. This analysis determined the association of the presence or absence of the tumor with the prognosis in each voxel after adjusting for the covariates. The study included 769 participants of 464 men and 305 women (mean age, 63years ± 12 [standard deviation]). The hazard ratio map indicated that tumors in the medial frontobasal region and around the third and fourth ventricles were associated with poorer prognoses, underscoring the challenges of complete resection and treatment accessibility in these areas regardless of the tumor volume. Conversely, tumors located in the right temporal and occipital lobes had favorable prognoses. This study showed an association between tumor location and prognosis. These findings may assist clinicians in developing more precise and effective treatment plans for patients with glioblastoma to improve their management.

When Would Minimally Invasive Spinal Surgery Not Be Preferable for Metastatic Spine Disease?

Metastatic spine tumor surgery (MSTS) is an important treatment modality of metastatic spinal disease (MSD). Open spine surgery (OSS) was previously the gold standard of treatment till the early 2010s. However, advancements in MSTS in recent years have led to the advent of minimally invasive spinal surgery (MISS) techniques for the treatment of MSD. The clear benefits of MISS have resulted in a current paradigm shift toward today's gold standard of MISS and early adjuvant radiotherapy in treating MSD patients. Nonetheless, despite improvements in surgical techniques and the rise of literature supporting MISS for MSD, there are still certain situations whereby MISS is not desirable or even suitable. There has also yet to be any literature describing the considerations of not using MISS in MSD in today's clinical context. A narrative review was conducted for this manuscript. All studies related to OSS and MISS in MSTS were included. A total of 54 studies were included in this review. These studies discussed various advantages of MISS for MSD in today's clinical context, including the patient profile, location of vertebrae involved with metastasis requiring treatment, tumor characteristics, as well as equipment availability. This study establishes situations in which MISS can be less applicable despite the advantages it may confer over traditional OSS. MSTS should be individualized, depending on the experience of the surgeon. OSS is a time-tested approach that still holds weight in MSTS and should be readily utilized depending on the clinical situation.

Multidisciplinary tumor boards in oral cavity cancer: survival effect due to balancing guideline adherence and treatment delays.

The purpose of the study was to assess the impact of a pretherapeutic Multidisciplinary Tumor Board (MTB) presentation on the prognosis and treatment outcomes in patients with primary oral cavity carcinoma. This single-center study included 630 patients diagnosed with oral cavity carcinoma treated between 2010 and 2020. The study cohort was divided in a group with and without pretherapeutic MTB presentation. Data on patient demographics, tumor characteristics, treatment and the time to treatment initiation (TTI) were collected retrospectively. Primary findings revealed no significant difference in 3-year survival rate (3-YSR) and 3-year disease-free survival rate (3-YDFSR) for the non-MTB and MTB group. The 3-YSR was 73.1% in the non-MTB group and 67.1% in the MTB group (p = 0.112). The 3-YDFSR was 73.8% in the non-MTB group and 76.5% in the MTB group (p = 0.447). Estimated mean 5-year survival (5-YS) and 5-year disease-free survival in (5-YDFS) did not differ significantly between both groups, across the UICC stages I-IV, as well as for the entire cohort. The TTI was significantly longer in the MTB group (33.5 days, CI: 31.3;35.7) compared to the non-MTB group (20.1 days, CI: 17.9;22.4, p < 0.001). The MTB group adhered more frequently to the national guidelines (68% vs. 79.6%, p < 0.01). The results demonstrate both positive and negative side effects of the MTB presentation in patients with oral cavity cancer. Further multicenter studies will be required to assess the impact of TTI and adherence to guidelines on the survival of oral cavity cancer patients.

Endonasal surgery high-risk carotid injury timeout checklist: implementation, institutional protocol and experience.

Carotid artery injury is a rare, but major complication of endonasal operations. The morbidity and mortality of such a complication can be mitigated by preparedness and a clear plan set in place to address the hemorrhage expeditiously. This study examines the implementation of such a carotid injury timeout checklist and demonstrates its effectiveness in a patient with possible arterial injury. A carotid injury timeout checklist was implemented for high risk endonasal procedures. The case selection was left to the surgeon, with guidelines including prior surgery, prior radiation, invasive tumors, and certain pathologies such as meningioma or chordoma. Factors affecting implementation were analyzed including tumor characteristics and patient history. Over a 12-month period, 103 endonasal operations were performed since the carotid artery injury timeout checklist was implemented, with 21 (20.4%) having a carotid artery injury timeout performed. Tumor characteristics that were associated with performing this timeout included Knosp grade (for pituitary adenomas, p = 0.002), carotid artery encasement (p < 0.001), extended approach (p < 0.001), tumor size (p = 0.05) and diagnosis (p < 0.001). Re-operation and prior radiation were not factors for this cohort. The single carotid artery branch (hypertrophic vidian artery) injury that was sustained was easily and successfully managed, aided by preparation established via this protocol. The additional time necessary for this timeout to be performed was negligible with respect to the overall surgery length. A carotid artery injury timeout can and should be successfully implemented for extended endonasal operations for pituitary and parasellar tumors with high risk factors including, but not limited to, carotid injury encasement, large tumor size and non-adenomatous diagnoses. A comprehensive plan for both intraoperative and perioperative management of the carotid injury is necessary to minimize the risk of morbidity and to deliver care expeditiously.

Assessment of oral disease burden among head and neck cancer patients in the Merseyside region.

Introduction Head and neck cancer (HANC) significantly impacts the oral cavity and dental health issues may complicate cancer treatment and post-treatment quality of life. Pre-treatment dental evaluation is critical for identifying and managing existing oral health problems. However, limited literature exists on the dental health status of patients at the time of HANC diagnosis. This study aims to address this gap and emphasise the importance of dental care in the management of HANC.Methods A retrospective analysis of medical records was conducted on patients scheduled for radiotherapy for HANC. Data on demographic characteristics, tumour characteristics and dental exam findings were extracted from the patient record.Results Of the 191 included patients, the average age was 62.9 years (SD: 10.09), with 80% being men. The prevalence of dental disease revealed 59% of cases presenting with unstable periodontal disease and an average decayed, missing, and filled teeth score of 19.9. Two-thirds of patients exhibited one or more carious lesions.Conclusion This retrospective study sheds light on the dental health status of patients with HANC at their pre-treatment evaluation. The high prevalence rates of dental caries and unstable periodontal disease highlight the importance of dental evaluation and intervention as part of the overall management of HANC patients.

Evolving molecular classification of aggressive B-cell lymphoma.

This review aims to provide an overview of the latest developments in the classification and molecular understanding of aggressive B-cell lymphomas, specifically focusing on diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL). Advances in molecular techniques have led to novel ways to classify these lymphomas based on clinical, histological, transcriptional, and genetic properties. While these methods have predominantly focused on the malignant compartment, recent studies emphasize the value of profiling the tumour microenvironment for a more comprehensive disease classification. Additionally, the integration of liquid biopsies represents a promising advancement, offering less invasive and dynamic insights into tumour characteristics and treatment response. Although molecular profiles are not yet routinely used to guide therapy, emerging data highlight their potential to predict responses to novel treatments. It is our belief that integrating molecular profiling and liquid biopsies into clinical practice and research now will pave the way for more personalized and effective therapies in the future.

Feasibility assessment of using cRISPR-Cas9 to improve the infiltration of CAR-T cells in solid tumors

Abstract. Chimeric antigen receptor T-cell immunotherapy (CAR-T) has been developing for decades, CAR-T is playing an increasingly important role in tumor treatment. However, because fibroblasts (CAFs) in solid tumors secrete proteins and glycans to form ECM, CAR-T is faced with the challenge of improving tumor invasion. To this end, a new scheme was put forth to alter CAR T cells such that they release heparinase (HPSE) to break down heparan sulfate proteoglycan (HSPG), which is covered on the outermost layer of the cancerous cells by CAF and released. In order to solve the above problems, CRISPR-Cas9 was proposed to modify CAR T to enhance the secretion of HPSE. Although this method has the advantage of broad spectrum, it still has certain defects. The matrix characteristics of different solid tumors and the subpopulations and regulatory mechanisms of HPSE need to be further studied. The off-target effects of CRISPR-Cas9 gene editing technology and the high cost and time-consuming problems of flow cytometry also limit its application. It is anticipated to enhance cell infiltration in solid tumors, boost CAR-T therapy's effectiveness in treating solid tumors, and advance the field of CAR-T therapy.

RETROSPECTIVE ANALYSIS OF GLIOBLASTOMA OUTCOMES

Background Glioblastoma (GBM) is one of the most aggressive brain cancers, with a median overall survival (OS) of about 15 months. This retrospective study focuses on 144 GBM cases treated over 12 years in our clinic in Romania, analyzing factors affecting progression-free survival (PFS) and OS, including genetic markers and treatment modalities. Methods This study involved patients treated between 2012 and 2024 at the National Institute of Neurology and Neurovascular Diseases in Bucharest. The cohort included 144 patients, with variables such as age, gender, tumor location, IDH mutation status, Karnofsky Performance Status (KPS), and genetic markers (MGMT methylation and EGFR amplification) analyzed. Survival outcomes were evaluated using Kaplan-Meier curves and log-rank tests. Results - Patient Demographics: The cohort included 64 males (44.4%) and 80 females (55.6%) with a mean age of 60.7 years. - Tumor Characteristics: The most common tumor location was the frontal lobe (31.9%), followed by multilobular GBM (26.3%). Right-side tumors were more prevalent (51.3%). - Genetic Markers: MGMT promoter was methylated in 46 patients (31.9%), and EGFR was amplified in 76 patients (52.7%). - Treatment Modalities: 105 patients (72.9%) received chemotherapy with temozolomide (TMZ), and 116 patients (80.5%) underwent radiotherapy. - Survival Outcomes: Median PFS was 5 months, and median OS was 8.5 months. Kaplan-Meier survival curves indicated significantly increased OS in patients with MGMT methylation undergoing chemotherapy (p&lt;0.005) and radiotherapy (p&lt;0.005). Similarly, OS was significantly higher in patients without EGFR amplification receiving chemotherapy (p&lt;0.005) and radiotherapy (p&lt;0.005). Conclusion The study emphasizes the importance of MGMT methylation and EGFR amplification in predicting survival outcomes in GBM patients. Immediate postoperative adjuvant therapy significantly improves PFS and OS. The findings underscore the need for coordinated care and timely access to adjuvant therapies to enhance survival rates in GBM patients. Second surgical interventions also showed a survival benefit, highlighting their potential role as salvage therapy in recurrent GBM cases.

Epidemiology, trends, and survival of ocular and orbital rhabdomyosarcoma: a nationwide study in the USA (1996-2018) : Ocular and orbital rhabdomyosarcoma in the USA.

Rhabdomyosarcoma (RMS) is a rare malignancy that affects both children and young adults. Therefore, the current incidence and mortality rates of ocular and orbital rhabdomyosarcoma (ORMS) need to be clarified. We aimed to explore the epidemiology, trends, and survival outcomes of ORMS in the United States population spanning over two decades, from 1996 to 2018. We retrospectively reviewed 92,633 patients with ocular and adnexal malignancies and identified 640 ORMS cases from the North American Association of National Cancer Registries. Demographics, tumor characteristics, treatment modalities, and survival outcomes were analyzed. Most ORMS cases (71.7%) were reported in children aged-0-9 years. The age-adjusted incidence of ORMS was 0.1 per million population (ppm), with males demonstrating a higher incidence (0.12 ppm) than females (0.09 ppm). Whites had the highest incidence rate (0.11 ppm). Embryonal ORMS is the most common histological subtype. The incidence trend over the 22-year study period revealed a decline in ORMS from 0.124 to 0.076, in contrast with the incidence of whole-body RMS, which showed an insignificant increase. The 5-year relative survival rates of patients with ORMS were 89.7%, whereas the 10-year relative survival rate was 87.2%. The 5-year relative survival trend for ORMS increased but was insignificant. ORMS primarily affects young children and males, with the embryonal subtype being the most common. Despite the declining incidence, survival rates have remained stable, underscoring the need for further research on the risk factors, diagnostics, and management strategies to improve patient outcomes. What is known Ocular and Orbital Rhabdomyosarcoma (ORMS) predominantly affects children, especially males, and is the most frequent primary tumor in the orbit during childhood. The embryonal subtype is the most common histological subtype of ORMS. What is new A significant decline in the incidence of ORMS was observed over the 22-yearstudy period, in contrast to the overall incidence of whole-body rhabdomyosarcoma. It has a characteristic bigeminal distribution with a peak at 3-4 and another at 6 years. Patients receiving combined treatment modalities showed improved survival rates, while those undergoing surgery alone had poorer outcomes. Despite advancements in treatment, there has been no significant increase in the 5-year relative survival trends for ORMS.

Assisted reproductive technology, pregnancy and recurrent disease in melanoma patients: a 30-year single institution experience.

Objectives The aim of this study is to assess differences in melanoma recurrence between patients conceiving spontaneously versus those undergoing assisted reproductive technology (ART), to determine use of ART in post-melanoma patients and to examine the impact of counseling of this specific patient group. Design This study is a 30-year analysis including data from a single center questionnaire and a retrospective cohort study. Participants/Materials Women of childbearing age with a history of melanoma were requested to participate in our study. We selected patients who underwent either primary melanoma treatment or treatment of local / distant recurrence at our institute between 1994 and 2021. Each participant received a questionnaire and informed consent form. The questions concerned general health, primary tumor characteristics, utilization of ART, subsequent pregnancies and development of recurrent melanoma. Additional information was collected from the medical files. Setting The research was conducted in a dedicated oncology center and tertiary referral center for melanoma in The Netherlands. Methods Participants received the questionnaires by mail. Six weeks later a reminder was sent to non-responders. Analysis was performed using descriptive statistics. For comparisons between groups Chi-square tests were used. P-value was considered significant when below 0.05. A clinically relevant difference in recurrence rate was defined as a 10% difference. Results A total of 498 questionnaires were available for analyses, 449 from living patients and 49 from relatives of diseased patients. One hundred and seventy-nine patients (36%) with a history of melanoma became pregnant following their diagnosis. In this group, 28 patients (16%) attempted to conceive using ART, and eight of them experienced disease recurrence. There was no difference in the recurrence rate between patients who became pregnant after the diagnosis of melanoma and those who never subsequently conceived (37% vs 35%, p=0.609). Limitations The main limitations of the study are its size, observational design and questionnaire methodology. Conclusions Pregnancy did not increase the risk of recurrent melanoma. The group of patients conceiving after ART was small and therefore it is difficult to confidently conclude that the recurrence risk is comparable to the other groups. Prospective international registration of these patients, their oncologic follow-up and possible use of assisted reproduction, will provide valuable information to determine any potential association between ART and risk of recurrent melanoma. This would enable health professionals to develop surveillance strategies and pre-conception counselling of patients wishing to conceive.

Developing a peripheral blood RNA-seq based NETseq ensemble classifier: A potential novel tool for non-invasive detection and treatment response assessment in neuroendocrine tumor patients receiving 177Lu-DOTATATE PRRT.

Neuroendocrine tumors (NETs) are presented with metastases due to delayed diagnosis. We aimed to identify NET-related biomarkers from peripheral blood. The development and validation of a multi-gene NETseq ensemble classifier using peripheral blood RNA-Seq is reported. RNA-Seq was performed on peripheral blood samples from 178 NET patients and 73 healthy donors. Distinguishing gene features were identified from a learning cohort (59 PRRT-naïve GEP-NET patients and 38 healthy donors). Ensemble classifier combining the output of five machine learning algorithms viz. Random Forest (RF), Extreme Gradient Boosting (XGBOOST), Gradient Boosting Machine (GBM), Support Vector Machine (SVM), and Logistic Regression (LR) were trained and independently validated in the evaluation cohort (n = 106). The response to PRRT was evaluated in the PRRT cohort (n = 46) and the PRRT response monitoring cohort (n = 16). The response to 177Lu-DOTATATE PRRT was assessed using RECIST 1.1 criteria. The Ensemble classifier trained on 61 gene features, distinguished NET from healthy samples with 100% accuracy in the learning cohort. In an evaluation cohort, the classifier achieved 93% sensitivity (95% CI: 87.8%-98.03%) and 91.4% specificity (95% CI: 82.1%-100%) for PRRT-naïve GEP-NETs (AUROC = 95.4%). The classifier returned >87.5% sensitivity across different tumor characteristics and outperformed serum Chromogranin A sensitivity (χ2 = 21.89, p = 4.161e-6). In the PRRT cohort, RECIST 1.1 responders showed significantly lower NETseq prediction scores after 177Lu-DOTATATE PRRT, in comparison to the non-responders. In an independent response monitoring cohort, paired samples (before PRRT and after 2nd or 3rd cycle of PRRT) were analyzed. The NETseq prediction score significantly decreased in partial responders (p = .002) and marginally reduced in stable disease (p = .068). The NETseq ensemble classifier identified PRRT-naïve GEP-NETs with high accuracy (≥92%) and demonstrated a potential role in early treatment response monitoring in the PRRT setting. This blood-based, non-invasive, multi-analyte molecular method could be developed as a valuable adjunct to conventional methods in the detection and treatment response assessment in NET patients.

HPB O01 - Colonization of bile with gammaproteobacteria reduces survival after surgery for pancreatic cancer in patients receiving gemcitabine-based adjuvant chemotherapy

Abstract Background Evidence suggests that the biliary microbiome influences the progression of pancreatic ductal adenocarcinoma (PDAC) in patients undergoing adjuvant chemotherapy. Specifically, Gammaproteobacteria (GPB) has been shown to have the potential to develop mutations which can metabolise gemcitabine into an inactive form. This study hypothesised that GPB influences survival in patients with PDAC undergoing adjuvant gemcitabine-based chemotherapy following surgery. Method This was a retrospective study of patients undergoing pancreatoduodenectomy from 2010 to 2020. Associations between patient and tumour characteristics, survival data, and results of intraoperative bile cultures (GPB+ or GPB-) were investigated. Analysis of patients matched by chemotherapy regimen and numbers of cycles of adjuvant therapy was also performed. Survival was analysed using Kaplan–Meier curves and Cox regression analysis. Results Analysis of 359 patients revealed that adjuvant gemcitabine-based therapy improved overall survival (OS). Patients who receive gemcitabine-based chemotherapy with a GPB+ biliary culture had a shorter OS compared to those who were GPB-, and a median survival of 17.9 vs 26.1 months, P=0.006. After matching for key chemotherapy variables, survival was greater in the GPB- group 26.8 vs 19.8, P=0.016. This association was not seen among patients who received no adjuvant therapy or non-gemcitabine based therapy. Conclusion Patients receiving gemcitabine-based chemotherapy after surgery are likely to have reduction in OS if they have a biliary culture positive for GPB.

MS O06 - HPB The ORDEAL Study: A National Survey of Surgeon Operative Preferences for Resection of Duodenal Adenocarcinoma

Abstract Background Duodenal adenocarcinoma (DA) accounts for over 50% of all small bowel adenocarcinomas, however there is a paucity of data on outcomes, no UK guidelines for surgical management, and current national standards of practice are unknown. There is ongoing debate whether long-term survival, perioperative outcomes, resection margin, and lymph node yield differ between pylorus-preserving pancreaticoduodenectomy (PPPD) and classical PD (cPD) in proximal DA (D1/D2), and between PD and limited resection (LR) in distal DA (D3/D4). The study aimed to discern current standards of practice and identify underlying reasons for operative preferences for proximal and distal DA. Method An anonymised survey was included as part of the registration form for a wider multicentre retrospective study looking at outcomes following resection for proximal and distal DA on Google Forms®. The survey was distributed via direct surgeon email correspondence, weekly newsletters and surgical society endorsement by PSGBI. Responses were collected between February-June 2024 and responses were analysed with quantitative and qualitative (inductive thematic analysis) methods. Results Responses were received from 61 surgeons across 27 centres. For proximal DA, surgeons are more likely to consider a classical Whipple’s (93.4%) compared to PPPD (29.5%). For distal DA, surgeons are equally likely to consider LR (73.8%) as PD (classical Whipple’s -37.7%, PPPD - 41%). These preferences have mostly remained consistent over time. Key themes identified from thematic analysis included oncological considerations, morbidity, surgeon preference, tumour characteristics, standards of practice, patient factors and anatomical considerations, with the former two themes being the most prominent. Conclusion For proximal DA, cPD is preferred over PPPD and for distal DA, LR and PD are equally considered, with oncological and morbidity considerations largely influencing decision making. This qualitative data will be compared to actual practice following completion of the wider ORDEAL study to identify discrepancies in practice and possible effect on patient outcomes.